1. Field of the Invention
This invention relates to a device and method for quantitative analysis of body fluid constituents. Specifically, this invention relates to a device and a method for quantitatively analyzing constituents of whole blood or other body fluids with self-contained, ready-to-use test strips and the process to manufacture the device.
2. Description of the Background Art
Medical science has an increasing need for quick, accurate determination of analytes in blood or other body fluids. Traditionally, assays for analytes have been performed by laboratories and required skilled technicians, complex apparatus and reagents, and considerable time in order to determine accurate results. Numerous qualitative and some quantitative devices and methods have been developed which eliminate or decrease the need for laboratory diagnostic services. Many of these devices and methods include test strips or dip sticks which can be exposed to blood or another body fluid in order to obtain a diagnostic result. A common example of this technology includes the various test products for determining the concentration of glucose in diabetics.
The determination of the concentration of glucose and other analytes has been performed by various devices and methods using either urine or blood as the body fluid sample. The most common of these tests are dip sticks for testing the concentration of glucose in urine. The dip sticks are dipped into a sample of urine and then undergo a color change. The color of the dip stick is compared to a chart of color references on the label of the container providing the dip stick. When the color of the dip stick is matched to the color reference, one determines the approximate glucose concentration from the color reference. Similar tests exist wherein paper strips are used to determine the concentration of glucose in whole blood. These tests are also conducted by comparing the amount of color formation of the paper strip to a standard. These semi-quantitative tests do not accurately determine the concentration of an analyte in the blood being tested unless an instrument is used.
U.S. Pat. No. 4,435,504 to Zuk, et al., discloses an immunochromatographic assay with support having bound "MIP" or antibody and a second enzyme. This invention measures the amount of analyte in a sample solution of a body fluid by combining a premeasured volume of sample with a premeasured volume of a solution of enzyme labelled analyte and immunochromatographing the solution or employing a combination of enzymes wherein one enzyme is the label and the other enzyme is affixed to the chromatographic support. The assay of this invention is performed by contacting the immunochromatograph with the sample containing solution. The sample traverses a region of the immunochromatograph by elution or solvent transport. The device used in this assay has a region in which the antibody is non-diffusively bound to a bibulous support. The analyte from the sample and its enzyme labelled conjugate traverse this zone along with the solvent. The analyte and its enzyme labelled analogue become bound to the support through the intermediacy of antibody complex formation. The signal producing system provides the area in this region with a color change which identifies the distance from a predetermined point over which the analyte and its enzyme labelled conjugate have traveled. In this manner, a quantitative determination of the analyte can be made. This invention does not directly test whole blood and requires accurate volumetric measurement of the sample and the enzyme conjugate solution and dilution of the sample by a separately applied solvent. Furthermore, the determination of the analyte concentration with this invention requires the use of a separate "signal producing system". The invention of this disclosure does not provide an immediate determination of the concentration of an analyte.
U.S. Pat. No. 4,594,327 to Zuk discloses an assay method for whole blood samples. This invention uses at least one specific binding pair which is substantially, uniformly bound to a solid bibulous element. The method to use this invention requires that the sample be mixed in an aqueous medium with a binding agent. This invention also requires a separate signal producing system such as that discussed for the patent above. The invention of this disclosure does not provide a self-contained unit that accurately determines the quantitative concentration of an analyte without the use of additional solvents or reagents.
An article by Sloan, et al., discloses "The Quantab Strip in the Measurement of Urinary Chloride and Sodium Concentrations" CLIN. CHEM. 30 (10), 1705-1707 (1984). The test strip of this disclosure provides a quantitative measurement of chloride and sodium concentrations in urine. The test strips of this disclosure rely on wicking alone and do not provide an additional capillary channel to speed up the process. The porous matrix typically requires between 15 to 30 minutes to draw urine up the entire measurement zone. The device of this article does not provide a rapid quantitative test, a channel or a separation means for solids.
U.S. Pat. Nos. 3,964,871 and 4,042,329 to Hochstrasser disclose a method and device for detecting either glucose or cholesterol. The device of these disclosures is dipped into a sample of body fluid. The fluid reacts with an analyte. The concentration of the analyte correlates with a color intensity scale which translates into an approximate quantitative determination of the analyte. The device of these disclosures does not provide an accurate, sensitive quantitative test for analytes.
U.S. Pat. No. 4,761,381 to Blatt et al. discloses a volume metering capillary gap device for applying a liquid sample onto a reactive surface. The device of this patent controls a liquid volume flowing onto a reactive surface by use of an overflow chamber. The capillary channel leading to the overflow chamber is controlled so that liquid cannot flow back into a reaction chamber. The method of analysis conducted by the Blatt et al. invention introduces liquid very quickly into the device (within 2 seconds) in order to prevent slow entry by simultaneous capillary action in the channel and wicking through the porous matrix at the bottom of the device. The geometry of the detection chamber determines the volume used for the test. Blatt et al. have two compartments connected "in parallel" to the sample entry port, i.e., liquid flowing from the entry port into the overflow chamber does not flow through the reaction chamber. The geometry of their reaction chamber, though rectangular, is not channel or appropriate for a measurement scale. This device can receive blood as a sample fluid, however, this device has no means for separating the cells from the plasma.
U.S. Pat. No. 4,756,884 to Hillman, et al., discloses a capillary flow device. The device provides for measuring a sample, mixing the sample with reagents, defining a flow path, and reading the result. The capillary tube of this device provides the sole driving source for the movement of liquid through the device. The use of this device primarily involves tests requiring blood agglutination and optical readers to determine test results. This device does not provide a self-contained quantitative analysis device for measuring analytes.
U.S Pat. No. 4,477,575 to Vogel et al. discloses a process and composition for separating plasma and serum from whole blood. This invention uses a composition of glass fibers having an average diameter of from 0.2.mu. to 0.5.mu. and a density of 0.1 g/cm.sup.2 to 0.5 g/cm.sup.2. The total volume of the plasma or serum separated from the blood is limited to at most 50% of the absorption volume of the glass fiber layer. Other fibers are disclosed as being useful in forming the composition with the glass fiber. The test devices disclosed in this patent do not meter plasma flow through the device nor provide a quantitative analysis of an analyte.
The industry lacks a device for quantitative analysis of constituents of whole blood or other body fluids that is fast, accurate, and completely self-contained.